University of Michigan

University of California

Oncosis

Other

Cyntellect, Inc.

Intrexon Corporation

Aastrom Biosciences, Inc.

Danmarks Tekniske Universitet

Forster, Jochen

Nielsen, Jens B.

Bernhard O Palsson

Michael F Clarke

Stephen G Emerson

Timothy M Eisfeld

Manfred Koller

Richard Schwartz

R Douglas Armstrong

Jeremy S Edwards

Alice S Chuck

Jochen Förster

Jens Bredal Nielsen

Imandokht Famili

Markus W Covert

Pengcheng Patrick Fu

Markus Herrgard

Adam M Feist

Victor C Yang

Robert H Bartlett

James Maluta

Elie G Hanania

Bjørn Gunnar Voldborg

Neema Jamshidi

Vasiliy A Portnoy

Pep Charusanti

Minoo Javanmardian

Robert A O'Neal

Lasse Ebdrup Pedersen

Robert O'Neal

Robert A O'NEAL

Manfred R Koller

Pengcheng Fu

Jochen Forster

Timothy Eisfeld

The present invention relates to mammalian cells modified to provide for improved expression of a recombinant protein of interest. In particular, the invention relates to CHO cells and other host cells in which the expression of one or more endogenous secreted proteins has been disrupted, as well as to the preparation, identification and use of such cells in the production of recombinant proteins.

Engineered mammalian cells for production of recombinant proteins

The invention provides mutantcells that contain one or more mutations in one or more of the rpoB, hns/tdk, cor A, ygaZ, iap, metL, ygeW, and pyrE/rph genes (exemplified in Table 2A and 2B), which confer on the mutant in M9-glucose minimal media the phenotype of increased level of growth and/or increased glucose uptake rate and/or increased acetate production rate and/or increased biomass yield, compared to a control(such as wild type) that lacks the one or more mutations in the one or more genes.

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Microbial strains with desirable carbohydrate productions characteristics and methods of making and using the same are provided herein.

Metabolic engineering of microbial organisms

The present invention describes a method to generate new chemical entities (NCEs) that have well-defined activities such as, but not limited to, anti-bacterial, antifungal and anthelmintic effects. The NCEs are generated through adaptive evolution of one microbe (the producer) against another organism or cell type (the target). The producer is made to compete against the target over time by co-culturing the two together and serially passing the producer organism until the producer adaptively evolves by synthesizing an NCE(s) that inhibits growth of or kills the target. The molecular structure of the chemical entity (or entities) is then elucidated using tools from genomics, molecular biology, computational biology, analytical chemistry, organic chemistry and related fields.

Method to generate novel bioactive molecules

The invention provides transgeniccells comprising a mutation in cydAB gene, and/or cyoABCD gene, and/or cbdAB gene, and/or ygiN gene, wherein the mutation reduces (preferably, but not necessarily, by 100%) the cytochrome oxydase activity of a protein encoded by cydAB gene, and/or cyoABCD gene, and/or cbdAB gene, and/or ygiN gene. In a preferred embodiment, the mutation is a deletion of the cydAB gene, cyoABCD gene, and cbdAB gene. In another embodiment, the mutation is a deletion of the cydAB gene, cyoABCD gene, cbdAB gene, and ygiN gene. In another embodiment, the transgeniccell, which comprises a deletion of cydAB gene, and/or cyoABCD gene, and/or cbdAB gene, and/or ygiN gene a) has substantially the same level of growth in oxic conditions as the level of growth in anoxic conditions ofthat lacks said deletion of cydAB gene, and/or cyoABCD gene, and/or cbdAB gene, and/or ygiN gene, and b) is capable of converting glucose to D-lactate and/or amino acid and/or 2,3-butanediol (2,3-BDO) under one or both of oxic conditions and anoxic conditions.

This invention provides a computational approach to identifying potential antibacterial drug targets based on a genomic sequence and its annotation. Starting from a fully sequenced genome, open reading frame assignments are made which determine the metabolic genotype for the organism. The metabolic genotype, and more specifically its stoichiometric matrix, are analyzed using flux balance analysis to assess the effects of genetic deletions on the fitness of the organism and its ability to produce essential biomolecules required for growth.

Methods for identifying drug targets based on genomic sequence data

This invention provides a computational approach to identifying potential antibacterial drug targets based on a genome sequence and its annotation. Starting from a fully sequenced genome, open reading frame assignments are made which determine the metabolic genotype for the organism. The metabolic genotype, and more specifically its stoichiometric matrix, are analyzed using flux balance analysis to assess the effects of genetic deletions on the fitness of the organism and its ability to produce essential biomolecules required for growth.

This invention provides a method and apparatus for selectively identifying, and targeting with an energy beam, specific cells within a cell population, for the purpose of inducing a response in the targeted cells. Using the present invention, every detectable cell in a population can be identified and affected, without substantially affecting non-targeted cells within the mixture.

Method and apparatus for selectively targeting specific cells within a cell population

Embodiments of the present invention generally relate to the construction, analysis, and characterization of dynamical states of biological networks at the cellular level. Methods are provided for analyzing the dynamical states by constructing matrices using high-throughput data types, such as fluxomic, metabolomic, and proteomic data. Some embodiments relate to an individual, while others relate to a plurality of individuals.

Methods and systems for genome-scale kinetic modeling

The invention provides an apparatus for electromagnetically affecting a particle of interest in a specimen. The apparatus includes (a) a stage capable of supporting the specimen; (b) a detector including at least one camera, wherein the detector is capable of resolving a particle of interest within the specimen; (c) a means for locating the particle of interest in three dimensions; (d) a means for focusing electromagnetic radiation to a focal volume within the specimen; and (e) a means for adjusting the relative positions of the stage and electromagnetic radiation focusing means, thereby positioning the particle of interest within the focal volume.

Method and device for selectively targeting cells within a three-dimensional specimen

The invention provides an in silico model for determining aphysiological function. The model includes a data structure relating a plurality ofreactants to a plurality ofreactions, a constraint set for the plurality ofreactions, and commands for determining a distribution of flux through the reactions that is predictive of aphysiological function. A model of the invention can further include a gene database containing information characterizing the associated gene or genes. The invention further provides methods for making an in silicomodel and methods for determining aphysiological function using a model of the invention.

The present invention relates to methods for achieving an optimal function of a biochemical reaction network. The methods can be performed in silico using a reconstruction of a biochemical reaction network of a cell and iterative optimization procedures. The methods can further include laboratory culturing steps to confirm and possibly expand the determinations made using the in silico methods, and to produce a cultured cell, or population of cells, with optimal functions. The current invention includes computer systems and computer products including computer-readable program code for performing the in silico steps of the invention.

Method for the evolutionary design of biochemical reaction networks

The present invention provides a method of refining a biosystem reaction network. The method consists of: (a) providing a mathematical representation of a biosystem; (b) reconciling said mathematical representation of said biosystem; (c) determining differences between observed behavior of a biosystem and in silico behavior of said mathematical representation of said biosystem under similar conditions; (d) modifying a structure of said mathematical representation of said biosystem, and (e) determining differences between said observed behavior of said biosystem and in silico behavior of said modified mathematical representation of said biosystem under similar conditions.

Methods and systems to identify operational reaction pathways

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La Jolla, CA, United States of America

Bernhard O Palsson